Stannyl radical-mediated cleavage of pi-deficient heterocyclic sulfones. Synthesis Of alpha-fluoro esters

Treatment of ethyl 2-(pyridin-2-ylsulfonyl)hexanoate with tributylstannane and azobis(2-methyl-2-propanitrile) (AIBN) in benzene at reflux for 36 h resulted in hydrogenolysis to give ethyl hexanoate (60%), whereas no reaction was observed after 48 h at reflux with ethyl 2-(phenylsulfonyl)hexanoate. Ethyl 2-(pyrimidin-2-ylsulfonyl)hexanoate underwent quantitative hydrogenolysis within 1 h under these conditions. This represents a mild new methodology for removal of the synthetically useful sulfone moiety. Substitution of Bu(3)SnD for Bu(3)SnH gave access to alpha-deuterium-labeled esters. Treatment of the alpha-(pyrimidin-2-ylsulfonyl) enolates derived from several esters with Selectfluor gave high yields of the 2-fluoro-2-(pyrimidin-2-ylsulfonyl)alkanoates, which were smoothly desulfonylated [Bu(3)SnH (2 equiv)/AIBN/benzene/Delta] to give 2-fluoroalkanoates. "Catalytic" tin hydride, generated from tribuytltin chloride (0.15 equiv) and excess polymethylhydrosiloxane in the presence of potassium fluoride, also effected removal of the pi-deficient alpha-(pyrimidin-2-ylsulfonyl) moiety from acid derivatives in high yields. Desulfonylation is suggested to proceed via alkoxy ketyl-type radicals and tin enolates.     

Studies toward the synthesis of alpha-fluorinated phosphonates via tin-mediated cleavage of alpha-fluoro-alpha-(pyrimidin-2-ylsulfonyl)alkylphosphonates. Intramolecular cyclization of the alpha-phosphonyl radicals

Treatment of the alpha carbanions generated from several alpha-(pyrimidin-2-ylsulfonyl)alkylphosphonates with Selectfluor gave high yields of the alpha-fluoro-alpha-(pyrimidin-2-ylsulfonyl)alkylphoshonates, which were desulfonylated [Bu(3)SnH/2,2'-azobisisobutyronitrile (AIBN)/benzene or toluene/Delta] to give alpha-fluoroalkylphosphonates. "Catalytic" tin hydride, generated from tributyltin chloride and excess polymethylhydrosiloxane in the presence of potassium fluoride, also effected removal of the pi-deficient alpha-(pyrimidin-2-ylsulfonyl) group from the phosphonate esters. Substitution of Bu(3)SnD for Bu(3)SnH gave access to alpha-deuterium-labeled phosphonates. Prolonged treatment of alpha-(pyridin-2-ylsulfonyl)alkylphosphonate with excess Bu(3)SnH/AIBN or catalytic tin hydride also effected desulfonylation but in moderate yields. This represents a mild new methodology for removal of the synthetically useful pi-deficient heterocyclic sulfone moiety and an alternative route for the preparation of alpha-fluorinated phosphonates. Desulfonylation is suggested to proceed via attack of tin radical at an oxygen (or sulfur) atom of the sulfonyl group to give a stabilized alpha-phosphonyl radical intermediate. The latter was found to undergo 5-exo-trig ring closure to give the corresponding 2-methylcyclopentylphosphonates. Treatment of diethyl 1-bromohex-6-enylphosphonate with Bu(3)SnH/AIBN produced an analogous mixture of ring-closure products. Treatment of [(2-bromo-5- methoxyphenyl)(fluoro)(pyrimidin-2-ylsulfonyl)]methylphosphonate with Bu(3)SnH resulted in an intramolecular radical [1,5]-ipso substitution reaction and migration of the pyrimidinyl ring to give fluoro[5-methoxy-2-(pyrimidin-2-yl)phenyl]methylphosphonate.     

Antioxidant action of organic sulfites—II. Esters of sulfurous acid as primary antioxidants

The effect of esters of sulfurous acid as primary antioxidants was examined. Different aliphatic, aromatic, open-chain and cyclic sulfites were synthesized. The reactions of organic sulfites with RO₂ and RO radicals, the chain carriers of the autoxidation of hydrocarbons and polymers, were simulated by means of the thermal decomposition of azobisisobutyronitrile (AIBN) in the presence of oxygen and of di-tert-butylperoxalate (DTBPO). The reactivity of organic sulfites with 2-cyanoisopropylperoxyl radicals is low. Only aromatic sulfites are able to trap peroxyl radicals; however, they are not very effective primary antioxidants. The reactions of the organic sulfites with tert-butoxyl radicals generally lead to an increase in the rate of decomposition of DTBPO, as determined from rate constants measured at 50 °C. A decomposition of DTBPO induced by liberated tert-butyl radicals in the presence of alkyl sulfites is very probable. Alkyl sulfites and aromatic sulfites with aliphatic groups act mainly as hydrogen donors in reactions with alkoxyl and peroxyl radicals.     

Generation of Oxygen-Centered Radicals by Reaction of Nitrate Esters with Tri-n-Butyltin Hydride

Treatment of nitrate esters wilh tri-n-butyltin hydride and AIBN in benzene at reflux is a convenient way to generate oxygen-centered (alkoxyl) radicals.     

Radical reactions initiated by chelate complexes of transition metals. X. Catalytic decomposition of α,α′-azobisisobutyronitrile

The decomposition of αα′-azobisisobutyronitrile (AIBN) in the presence of bis(-)-ephedrine copper (II) chelate was studied in 1,3,5-trimethylbenzene. It was found that the chelate accelerated the decomposition of AIBN and at the same time interacted with the free radicals arising in the course of this process. The decomposition of AIBN as well as the decay of paramagnetic Cu⁺² particles is a reaction of order 0.3 with respect to the chelate and of order 1.3 and 1.1 with respect to AIBN, respectively. The activation energy of the AIBN decomposition in the presence of chelate is 13–22 kcal/mole for the molar ratio [AIBN]₀/[Chelate]₀ ranging from 1 to 100. On the basis of the kinetic results and analysis of reaction products the mechanism of the interaction of chelate with AIBN is discussed.     

Synthesis and radical fragmentation of carbohydrate anomeric nitrates. Formation of convenient chiral synthetic intermediates

A new procedure for the C1–C2 fragmentation of cyclic carbohydrates, through the formation of anomeric alkoxy radicals from the corresponding nitrate esters, with ⁿBu₃SnH/azobisisobutyronitrile (AIBN), affords acyclic alditols in good yields.     

Amides as precursors of imidoyl radicals in cyclisation reactions

Amides have been successfully used as precursors of imidoyl radicals for radical cyclisation. The amides have been converted to imidoyl selanides via reaction with phosgene to yield imidoyl chlorides followed by reaction with potassium phenylselanide. Imidoyl selanides were reacted with tributyltin hydride (Bu₃SnH) as the radical mediator with triethylborane or AIBN as initiators to yield imidoyl radicals for cyclisation reactions. Imidoyl radicals have been cyclised onto alkenes to yield 2,3-substituted-indoles and -quinolines and also onto pyrroles and indoles to give bi- and tricyclic heteroarenes.     

Trimethyl phosphite as a trap for alkoxy radicals formed from the ring opening of oxiranylcarbinyl radicals. Conversion to alkenes. Mechanistic applications to the study of C-C versus C-O ring cleavage

Trimethyl phosphite, (MeO)(3)P, is introduced as an efficient and selective trap in oxiranylcarbinyl radical (2) systems, formed from haloepoxides 8-13 under thermal AIBN/n-Bu(3)SnH conditions at about 80 degrees C. Initially, the transformations of 8-13, in the absence of phosphite, to allyl alcohol 7 and/or vinyl ether 5 were measured quantitatively (Table 1). Structural variations in the intermediate oxiranylcarbinyl (2), allyloxy (3), and vinyloxycarbinyl (4) radicals involve influences of the thermodynamics and kinetics of the C-O (2 --> 3, k(1)) and C-C (2 --> 4, k(2)) radical scission processes and readily account for the changes in the amounts of product vinyl ether (5) and allyl alcohol (7) formed. Added (MeO)(3)P is inert to vinyloxycarbinyl radical 4 and selectively and rapidly traps allyloxy radical 3, diverting it to trimethyl phosphate and allyl radical 6. Allyl radicals (6) dimerize or are trapped by n-Bu(3)SnH to give alkenes, formed from haloepoxides 8, 9, and 13 in 69-95% yields. Intermediate vinyloxycarbinyl radicals (4), in the presence or absence of (MeO)(3)P, are trapped by n-Bu(3)SnH to give vinyl ethers (5). The concentrations of (MeO)(3)P and n-Bu(3)SnH were varied independently, and the amounts of phosphate, vinyl ether (5), and/or alkene from haloepoxides 10, 11, and 13 were carefully monitored. The results reflect readily understood influences of changes in the structures of radicals 2-4, particularly as they influence the C-O (k(1)) and C-C (k(2)) cleavages of intermediate oxiranylcarbinyl radical 2 and their reverse (k(-1), k(-2)). Diversion by (MeO)(3)P of allyloxy radicals (3) from haloepoxides 11 and 12 fulfills a prior prediction that under conditions closer to kinetic control, products of C-O scission, not just those of C-C scission, may result. Thus, for oxiranylcarbinyl radicals from haloepoxides 11, 12, and 13, C-O scission (k(1), 2 --> 3) competes readily with C-C cleavage (k(2), 2 --> 4), even though C-C scission is favored thermodynamically.     

Iminyl radicals from alpha-azido o-iodoanilides via 1,5-H transfer reactions of aryl radicals: new transformation of alpha-azido acids to decarboxylated nitriles

The radical reaction of tributyltin hydride with o-iodo- N-methylanilides derived from alpha-azido acids provides an excellent access to alpha-(aminocarbonyl)iminyl radicals through 1,5-hydrogen transfer reaction of initially formed aryl radicals followed by beta-elimination of dinitrogen from ensuing alpha-azido-alpha-(aminocarbonyl)alkyl radicals. The outcoming iminyls display a peculiar tendency to form corresponding nitriles by beta-elimination of aminocarbonyl radicals.     

Syntheses and polymerization of (meth)acrylates containing spiro ortho ester moieties

Acrylates and methacrylates bearing pendant spiro ortho ester groups ( 3 ) were prepared by the reaction of (meth)acrylic acid with bromomethyl spiro ortho esters ( 2 ) in the presence of 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU). These monomers were copolymerized with styrene (St) at 60°C in the presence of α,α'-azobisisobutyronitrile (AIBN) to give the corresponding copolymers with M?_n 6000-17000 and their compositions were in proportion to the feed ratios. Similarly, the copolymerization of 3 with acrylonitrile (AN) was carried out at 60°C to obtain the corresponding copolymers with the similar compositions to the feed ratios. Two kinds of 3 -St copolymers with different compositions were treated with BF₃OEt₂ in refluxing methylene dichloride affording the crosslinked polymers quantitatively. Slight expansion in volume was observed during the crosslinking.     

(endo)-5-(2-haloethyl)-2-norbornene. A new radical probe.

(endo)-5-(2-haloethyl)-2-norbornenes have been synthesized, and their corresponding radicals generated by reaction with sodium, magnesium, sodium naphthalenide and tri-n-butyltin hydride in the presence of AIBN to produce both straight chain and cyclized products. This probe cyclizes substantially faster than the often used 5-hexenyl halide probes.     

A facile route to vinyl- and arylphosphonates by vinyl and aryl radical trapping with (MeO)3P

The generation of vinyl or aryl radicals under classical, thermal AIBN/n-Bu(3)SnH conditions at 80 degrees C in the presence of an excess of (MeO)(3)P gives rise to the corresponding vinyl- or arylphosphonates in good yields. This approach complements the photochemical reactions of the same systems previously used. Reactions with the individual stereoisomers of MeCH=CHMeBr (thermal AIBN/n-Bu(3)SnH conditions) afford a radical-equilibrated 96/4 E/Z ratio of vinylphosphonates. Substitution of (TMS)(3)SiH for n-Bu(3)SnH yields an approximately 1/1 ratio of separable E and Z vinylphosphonate diastereomers.     

The role of tin(II) octoate – azobisisobutyronitrile complex in the formation rate of the respective networks in simultaneous interpenetrating polymer networks

Simultaneous interpenetrating polymer networks (IPNs) based on polyether polyurethane (PUR) and poly(methyl methacrylate‐co‐trimethylol‐propane trimethacrylate) (PMMA) were prepared in bulk at 60°C, using tin(II) octoate and azobisisobutyronitrile (AIBN) as pur polymerization catalyst and free‐radical initiator, respectively. The kinetics of the PUR network formation, PMMA network formation as well as PUR/PMMA IPN formation were studied independently by Fourier transform infra‐red spectroscopy. The simultaneous formation of the two networks interfered with each other, although they follow different polymerization mechanisms. Mainly two effects concerning the free‐radical polymerization have been seen: a decrease of the initiation period and an earlier appearance of the Trommsdorff effect when increasing the concentration of the catalyst. On the other hand, the presence of AIBN in the reaction medium drastically reduced the catalytic efficiency of the organotin compound. An explanation of these results for this particular activating system could be the formation of a cyclic equimolar complex by coordination of the nitrile groups of AIBN with the Sn(II) atom. Complexation both reduces the effective catalyst concentration and induces steric constraints in the azo bond of AIBN, rendering this linkage weaker and more easily cleavable and allowing an early decomposition into radicals of the complexed AIBN. The maximum rate corresponds to a 1:1 complex. Further, decomposition into radicals leads to tin oxidation and formation of a new tetravalent organotin compound, the catalytic activity of which is lower than that of pure tin(II) octoate for the isocyanate‐alcohol reaction.     

Termination of Mn(III)-based oxidative cyclizations by trapping with azide

The radicals formed in Mn(III)-based oxidative free-radical cyclizations of beta-keto esters and malonate esters can be trapped with sodium azide and Mn(III) to give cyclic and bicyclic azides in 30-80% yield. Reduction of the azide gives bi- and tricyclic lactams. [reaction: see text]     

Thermal polymerization of styrene in the presence of some ferrocene derivatives. II. Low concentrations of vinylferrocene and ethylferrocene

Styrene has been polymerized thermally at 60°C in the presence of low concentrations of vinylferrocene and in the presence and absence of 2,2′-azobisisobutyronitrile (AIBN). The polymerizations were studied in bulk and also in benzene solution. The thermal polymerization of styrene in the presence of ethylferrocene, but without added AIBN or solvent, was also examined. The bulk polymerizations exhibited high initial rates of polymerization followed by a decrease in rate. Initial rates of polymerization for bulk polymerizations in the absence of AIBN have been interpreted by means of a kinetic scheme involving propagation with styrene participating in a specific interaction with the ferrocene derivative and some kinetic parameters associated with this scheme have been evaluated. The decrease in the rate of polymerization is due to the formation of a retarder. The benzene solution polymerizations fitted a simple kinetic scheme and the transfer constant for vinylferrocene with respect to polystyryl radicals C_s, has been evaluated as 1.98 × 10^?3.     

Mechanistic aspects of thiyl radical-promoted acyl radical cyclization of formylenoate-cyclization versus oxidation

Treatment of formylalkenoates 1 and 7 with 2,2'-azobis(2-methylpropanenitrile) (AIBN) in the presence of dioxygen gave oxygenated carboxylic acids 5, 6, 8, 9 instead of acyl radical cyclization products, through preferential reaction of the corresponding acyl radicals with dioxygen rather than intramolecular attack to an enoate moiety. The reaction of 1 with AIBN in the absence of dioxygen recovered starting 1 in 98% yield.     

The transformation of alkenes into γ-lactones using α-iodoesters

Iodostannyl esters react with alkenes in the presence of AIBN to afford γ-lactones.     

Asymmetric homologation of boronic esters bearing azido and silyloxy substituents

In the asymmetric homologation of boronic esters with a (dihalomethyl)lithium, substituents that can bind metal cations tend to interfere. Accordingly, we undertook the introduction of weakly basic oxygen and nitrogen substituents into boronic esters in order to maximize the efficiency of multistep syntheses utilizing this chemistry. Silyloxy boronic esters cannot be made efficiently by direct substitution, but a (hydroxymethyl)boronic ester has been silylated in the usual manner. Conversion of alpha-halo boronic esters to alpha-azido boronic esters has been carried out with sodium azide and a tetrabutylammonium salt as phase-transfer catalyst in a two-phase system with water and either nitromethane or ethyl acetate. These are safer solvents than the previously used dichloromethane, which can form an explosive byproduct with azide ion. Boronic esters containing silyloxy or alkoxy and azido substituents have been shown to react efficiently with (dihalomethyl)lithiums, resulting in efficient asymmetric insertion of the halomethyl group into the carbon-boron bond.     

Photolysis of alpha-azidoacetophenones: direct detection of triplet alkyl nitrenes in solution

We report the first detection of triplet alkyl nitrenes in fluid solution by laser flash photolysis of alpha-azido acetophenone derivatives, 1. Alphazides 1 contain an intramolecular triplet sensitizer, which ensures formation of the triplet alkyl nitrene by bypassing the singlet nitrene intermediate. At room temperature, azides 1 cleave to form benzoyl and methyl azide radicals in competition with triplet energy transfer to form triplet alkyl nitrene. The major photoproduct 3 arises from interception of the triplet alkyl nitrene with benzoyl radicals. The triplet alkyl nitrene intermediates are also trapped with molecular oxygen to yield the corresponding 2-nitrophenylethanone. Laser flash photolysis of 1 reveals that the triplet alkyl nitrenes have absorption around 300 nm. The triplet alkyl nitrenes were further characterized by obtaining their UV and IR spectra in argon matrices. (13)C and (15)N isotope labeling studies allowed us to characterize the C-N stretch of the nitrene intermediate at 1201 cm(-)(1).     

Photochemistry of Thiophen-2(5H)-ones

Mechanistic evidence for the light-induced ring opening of thiophen-2(5H)-ones 1 in alcohols affording α, β-unsaturated mercapto esters 2 is presented. Regio-and stereochemical aspects of the ring closure of alkenylthio (type 3 ) radicals 15 and 17 to S-heterocycles 16 and 18 , of 3-thiahex-5-enyl radicals 4 to (tetrahydrothien-3-yl)methyl radicals 6 and of (2,3-dihydrothien-3-yl)methyl radicals 30 (type 7, but-3-enyl radicals) to cyclopropane-methyl radicals 29 are discussed. Irradiation (λ 350 nm) of 1 in cyclohexane in the presence of 2,3-dimethylbut-2-ene affords [2 + 2] cycloadducts 14 albeit in very low yields.